Obestatin

Obestatin is a peptide hormone encoded by the ghrelin gene, which has been identified as having a variety of physiological roles, particularly in the regulation of appetite and metabolism. It is derived from the same precursor as ghrelin, but unlike ghrelin, which stimulates appetite, obestatin has been found to suppress food intake and influence a range of metabolic processes1. The discovery of obestatin has opened new avenues for understanding the complex mechanisms that regulate energy balance and has potential implications for the treatment of metabolic disorders such as obesity and diabetes26.

Obestatin exerts its effects through binding to the orphan G protein-coupled receptor GPR391. It has been shown to play a role in inhibiting jejunal contraction, reducing food intake, and decreasing body weight gain in rats1. In pancreatic β-cells and human islets, obestatin promotes cell survival and proliferation, and it has anti-apoptotic effects, particularly under stress conditions such as serum deprivation and cytokine treatment23. The peptide increases cAMP levels and activates key signaling pathways, including extracellular signal-related kinase 1/2 (ERK1/2) and phosphatidylinositol 3-kinase (PI 3-kinase)/Akt, which are involved in cell survival and function23. Additionally, obestatin has been shown to upregulate the expression of genes involved in β-cell function and insulin signaling, such as GLP-1R and IRS-223.

Metabolic Regulation

Obestatin has been implicated in the regulation of metabolism, with studies showing that it can inhibit glucose-induced insulin secretion in rats, suggesting a role in glucose homeostasis9. It also appears to have a role in lipid metabolism, as fragments of obestatin have been shown to modulate feed intake, circulating lipids, and stored fat7.

Cardiovascular Function

In the cardiovascular system, obestatin has demonstrated cardioprotective effects. It reduces infarct size and contractile dysfunction in isolated rat hearts subjected to ischemia-reperfusion and inhibits apoptosis in stressed cardiomyocytes5. These effects are mediated through the activation of signaling pathways such as PI3K and ERK1/25. Obestatin also has emerging therapeutic potential for diabetes-related cardiovascular complications6.

Neurological Effects

Obestatin has been found to improve memory performance and exert anxiolytic effects in rats, suggesting a role in cognitive function and stress response4. It influences learning and memory processes involving the hippocampus and amygdala4.

Fluid Homeostasis

The peptide has been shown to inhibit vasopressin secretion and thirst, indicating a physiological action in the control of fluid homeostasis8. This could have implications for the treatment of conditions associated with fluid imbalance.

Skeletal Muscle Repair

Obestatin promotes skeletal muscle regeneration after injury by stimulating satellite stem cell expansion and myofiber hypertrophy10. It also enhances microvascularization and may inhibit myostatin, a negative regulator of muscle growth, suggesting its potential as a therapeutic agent for muscle injuries and myopathies10.